3G9Y

Crystal structure of the second zinc finger from ZRANB2/ZNF265 bound to 6 nt ssRNA sequence AGGUAA

Summary for 3G9Y

• Entry DOI: 10.2210/pdb3g9y/pdb
• Related: 2k1p
• Descriptor: Zinc finger Ran-binding domain-containing protein 2, RNA (5'-R(*AP*GP*GP*UP*AP*A)-3'), ZINC ION, ... (4 entities in total)
• Functional Keywords: zinc finger, zranb2, znf265, rna, protein-rna complex, transcription-rna complex, transcription/rna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : O95218
• Total number of polymer chains: 2
• Total formula weight: 5763.84

Authors

Loughlin, F.E.,McGrath, A.P.,Lee, M.,Guss, J.M.,Mackay, J.P. (deposition date: 2009-02-15, release date: 2009-03-03, Last modification date: 2024-03-20)

Primary citation

Loughlin, F.E.,Mansfield, R.E.,Vaz, P.M.,McGrath, A.P.,Setiyaputra, S.,Gamsjaeger, R.,Chen, E.S.,Morris, B.J.,Guss, J.M.,Mackay, J.P.
The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5' splice site-like sequences
Proc.Natl.Acad.Sci.USA, 106:5581-5586, 2009

PubMed Abstract: The alternative splicing of mRNA is a critical process in higher eukaryotes that generates substantial proteomic diversity. Many of the proteins that are essential to this process contain arginine/serine-rich (RS) domains. ZRANB2 is a widely-expressed and highly-conserved RS-domain protein that can regulate alternative splicing but lacks canonical RNA-binding domains. Instead, it contains 2 RanBP2-type zinc finger (ZnF) domains. We demonstrate that these ZnFs recognize ssRNA with high affinity and specificity. Each ZnF binds to a single AGGUAA motif and the 2 domains combine to recognize AGGUAA(N(x))AGGUAA double sites, suggesting that ZRANB2 regulates alternative splicing via a direct interaction with pre-mRNA at sites that resemble the consensus 5' splice site. We show using X-ray crystallography that recognition of an AGGUAA motif by a single ZnF is dominated by side-chain hydrogen bonds to the bases and formation of a guanine-tryptophan-guanine "ladder." A number of other human proteins that function in RNA processing also contain RanBP2 ZnFs in which the RNA-binding residues of ZRANB2 are conserved. The ZnFs of ZRANB2 therefore define another class of RNA-binding domain, advancing our understanding of RNA recognition and emphasizing the versatility of ZnF domains in molecular recognition.

PubMed: 19304800
DOI: 10.1073/pnas.0802466106

Experimental method

X-RAY DIFFRACTION (1.4 Å)